Design, Synthesis, and Biological
Evaluation of -Ketosulfonamide
Adenylation Inhibitors as Potential
Antitubercular Agents
Jagadeshwar Vannada,Eric M. Bennett,Daniel J. Wilson,Helena I. Boshoff,Clifton E. Barry, III, andCourtney C. Aldrich*
Center for Drug Design, Academic Health Center, University of Minnesota,
Minneapolis, Minnesota 55455, and Tuberculosis Research Section,
National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852-1742
aldri015@umn.edu
Received July 13, 2006
Abstract:
The antitubercular nucleoside antibiotics 1 and 2 were recently described that inhibit the adenylate-forming enzyme MbtA and disrupt biosynthesis
of the virulence-conferring siderophore known as mycobactin in Mycobacterium tuberculosis. Herein, we report efforts to refine this inhibitor
scaffold by replacing the labile acylsulfamate linkage (highlighted) with the more chemically robust -ketosulfonamide linkage of 3 and 4.
-Ketosulfonamide
Adenylation Inhibitors as Potential
Antitubercular Agents
